The success in corneal transplantation has been related to a unique form of specialized antigen processing and immunosuppression leading to a deviant form of systemic alloimmunity known as anterior chamber- associated immune deviation (ACAID). Clinical and laboratory investigations suggest that ACAID can be abrogated in anterior segment insults leading to corneal neovascularization (CNV), the most significant risk factor in allograft rejection. A critical limitation in the study of CNV in corneal graft rejection has been the lack of standardization in induction and grading of CNV and outcome assessment. A series of experiments in mice is proposed that will measure corneal allograft survival and donor-specific DTH and CTL activation as functions of the degree of CNV. A precise, reproducible method for CNV induction/regression will be used to produce varying degrees of "risk". At specified preoperative time points, maneuvers designed to alter the degree of risk either physically (reducing the caliber and extent of CNV by inducing neovessel regression or using angiostatic steroids) or physiologically (inducing ACAID) will be performed in subgroups of animals. After keratoplasty, clinical graft survival and DTH and CTL activity will be compared among the subgroups. It is hypothesized that different degrees of CNV will have measurable effects on the outcome parameters; and that the degree of donor-specific DTH abrogation by preoperative ACAID induction can attenuate the destabilizing effect of CNV on the ocular microenvironment The longterm objective of this work is to contribute to the development of risk stratification and control schemes that would have utility in the laboratory as well as the clinical setting.